Research focus

​The group of Ludo Van Den Bosch focuses on the mechanisms of acute and chronic axonal and neuronal degeneration and regeneration, aiming to contribute to the development of new therapeutic strategies for neurodegenerative disorders. This group intensively studies motor neuron diseases (amyotrophic lateral sclerosis (ALS) and hereditary motor neuropathies), frontotemporal dementia (FTD) and stroke.

Both familial (autosomal dominant) and sporadic forms of ALS are known. Mutations in several genes are the cause familial ALS: SOD1, FUS and TDP-43 mutations being the most important ones, in addition to the recently discovered hexanucleotide repeats in the non-coding region of the C9orf72 gene.

The group investigates the role of excitotoxicity, phase transitions and stress granule formation, the contribution of non-neuronal cells and the therapeutic potential of nanobodies. Furthermore, the genetic contribution to the pathogenesis of ALS is a main topic of study. This group has developed a zebrafish and a Drosophila model to perform screenings for disease-modifying genetic factors. EphA4, histone deacetylase 6 (HDAC6) and factors involved in nucleocytoplasmic transport were discovered as important modifiers. Recently, the lab has established iPSC-derived motor neuron models to further investigate the disease mechanisms linked to these modifiers. In the future, these cells will also be used to investigate potential therapeutic strategies for ALS.

Axonal degeneration of the motor axon is the main characteristic of Charcot-Marie-Tooth disease and of distal hereditary motor neuropathy (distal HMN). The group of Ludo Van Den Bosch also focuses on the pathogenic mechanisms underlying these diseases, with a particular focus on HSPB1 and GARS. The research concentrates on the involvement of cytoskeletal modifications (and in particular alpha-tubulin acetylation) in the pathogenesis of these peripheral neuropathies. Also for this disease, the lab uses iPSC-derived motor neuron model to investigate disease mechanisms.

Both clinically and pathologically, there is a clear link between ALS and FTD. Familial forms of FTD can be caused by mutations in the progranulin gene and by hexanucleotide repeats in the C9orf72 gene. Moreover, TDP-43 aggregates are a hallmark of FTD. Therefore, the molecular relationship between these two disorders is studied by investigating the biology of progranulin, TDP-43 and C9orf72.

Finally, to elucidate the mechanisms underlying axonal regeneration, paradigms of acute neurodegeneration relevant to stroke and recovery from stroke are also a topic of study in this laboratory.

This research is being conducted by using both in vitro (glial and motor neuron cultures) and in vivo models (spontaneous, induced and transgenic models for acute and chronic neurodegeneration). Genetic and clinical studies are being performed in close relationship with the Department of Neurology at the University Hospitals Leuven.

Interested in the molecular mechanisms of ALS? Watch this beautiful animation Nature Reviews Disease Primers made based on input of the group of Ludo Van Den Bosch and Wim Robberecht (VIB-KU Leuven).nature.com/animations/ALS17

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News

04/03/2019 - Each year, the EU launches calls for postdoc research fellowships through the Marie Sklodowksa-Curie Actions. Fellowships provided through these actions support researchers regardless of age & nationality.

18/07/2018 - Using a newly developed fruit fly model, researchers led by prof. Ludo Van Den Bosch (VIB-KU Leuven) have zoomed in on the protein structure of FUS to gain more insight into how it causes neuronal toxicity and disease.

08/02/2018 - Inhibiting HDAC6 improves the structural stability of cells and protects against neuronal damage. Leuven research uncovered that targeting this mechanism could be a promising therapeutic approach for peripheral neuropathies.

30/06/2017 - A research team with Ludo Van Den Bosch at its helm has identified a new process that leads to the neurodegenerative brain diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

19/06/2017 - Researchers at VIB, KU Leuven, and UZ Leuven, in collaboration with researchers at the University of Jena, have demonstrated that measuring neurofilaments provides reliable confirmation of an ALS diagnosis.

08/05/2017 - ​In a recent study in Human Molecular Genetics, researchers from VIB and KU Leuven led by prof. Philip Van Damme, reveal a novel function for progranulin in lysosomes: it acts as chaperone of the lysosomal protease cathepsin D.

17/03/2017 - Led by professor Ludo Van Den Bosch (VIB-KU Leuven), scientists from Belgium, the UK and the US have identified new processes that form protein “clumps” that are characteristic of ALS and frontotemporal lobar degeneration (FTLD).

20/08/2016 - ALS & FTD are fatal, adult-onset neurodegenerative disorders. The group of Ludo Van Den Bosch and Wim Robberecht (VIB/KU Leuven) has discovered profound new insights into the causes of these diseases that will drive future research

14/07/2016 - Research into amyotrophic lateral sclerosis (ALS) conducted by VIB-KU Leuven has led to interesting and unexpected conclusions. This research was conducted in the VIB Laboratory of Neurobiology, led by professors Ludo Van Den Bosch and Wim Robberecht.